Search

Xue-Jun Wang,1,* Xiao-Ying Li,1,* Xiao-Cong Guo,1,* Li Liu,1 You-You Jin,1 Yun-Qiong Lu,1 Yao-Jia-Ni Cao,1 Jun-Yi Long,1 Huan-Gan Wu,2 Dan Zhang,2 Guang Yang,2 Jue Hong,2 Yan-Ting Yang,2 Xiao-Peng Ma1,2 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Yan-Ting Yang, Key Laboratory of Acupuncture-Moxibustion and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China, Email pengpengma@163.com; tcmyyt@126.comBackground: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn’s disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD.Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks.Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1.Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.Keywords: herb-partitioned moxibustion, Crohn’s disease, lncRNA, ceRNA, lncRNA LOC102550026/miR-34c-5p/Pck1 axis

Minyan Wei,1,2 Xiucai Guo,1,3 Liuxiao Tu,1 Qi Zou,1 Qi Li,1 Chenyi Tang,1 Bao Chen,1 Yuehong Xu,1 Chuanbin Wu1 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Guangzhou Medical University, 3Department of Pharmacy, 12th People’s Hospital of Guangzhou City, Guangzhou, People’s Republic of China Abstract: Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by μ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention. Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function, nutritional status, inflammatory response, and clinical outcomes of this special population has not yet been fully verified., Aim: To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer., Methods: This is a retrospective study, including 60 elderly gastric cancer patients aged 70 years and above, divided into a nutritional support group and a control group. The nutritional support group received full postoperative nutritional support, including individualized meal formulation, and intravenous and parenteral nutrition supplementation, and was regularly evaluated and adjusted by a professional nutrition team. The control group received routine postoperative care., Results: After intervention, the proportion of CD4+ lymphocytes (25.3% ± 3.1% vs 21.8% ± 2.9%, P < 0.05) and the level of immunoglobulin G (12.5 G/L ± 2.3 G/L vs 10.2 G/L ± 1.8 G/L, P < 0.01) were significantly higher in the nutritional support group than in the control group; the changes in body weight (-0.5 kg ± 0.8 kg vs -1.8 kg ± 0.9 kg, P < 0.05) and body mass index (-0.2 ± 0.3 vs -0.7 ± 0.4, P < 0.05) were less significant in the nutritional support group than in the control group; and the level of C-reactive protein (1.2 mg/L ± 0.4 mg/L vs 2.5 mg/L ± 0.6 mg/L, P < 0.01) and WBC count (7.2 × 10 9 /L ± 1.5 × 10 9 /L vs 9.8 × 10 9 /L ± 2.0 × 10 9 /L, P < 0.01) were significantly lower in the nutritional support group than in the control group. In addition, patients in the nutritional support group had a shorter hospital stay (10.3 d ± 2.1 d vs 14.8 d ± 3.6 d, P < 0.05) and lower incidence of infection (15% vs 35%, P < 0.05) in those of the control group., Conclusion: The intervention by the nutritional support team has a positive impact on postoperative immune function, nutritional status, inflammatory response, and clinical outcomes in elderly patients with gastric cancer., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold. The ligand designed with lipophilic small-sized scaffolds bearing multipositive charges targeting the unique feature of high mitochondrial membrane potential (MMP) is lacking and most mitochondria-selective ligands are not G4-targeting. Herein, we report a new small-sized dicationic lipophilic ligand to target MMP and mitochondrial DNA G4s to enhance drug delivery for anticancer. The ligand showed marked alteration of mitochondrial gene expression and substantial induction of ROS production, mitochondrial dysfunction, DNA damage, cellular senescence, and apoptosis. The ligand also exhibited high anticancer activity against HCT116 cancer cells (IC 50 , 3.4 μM) and high antitumor efficacy in the HCT116 tumor xenograft mouse model (∼70% tumor weight reduction).

Background and Purpose: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined., Experimental Approach: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test., Key Results: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit., Conclusions and Implications: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects., (© 2023 British Pharmacological Society.)

Microcystins (MCs) are the most widespread, frequently found, and seriously toxic cyanobacterial toxins in aquatic environments. Microcystin-leucine-arginine (MCLR) and microcystin-arginine-arginine (MCRR) are the most studied MCs. Normally, their levels are low and they coexist in the environment; however, they may also interact with each other. The developmental toxicity of MCLR in the presence of MCRR in the early life stage of zebrafish (from 2 to 120 h post fertilization) was investigated for the first time in this study. Our findings revealed that MCRR treatment marginally elevated thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels, whereas MCLR treatment alone resulted in a significant increase in T3 and T4 levels, indicating a cooperative effect. Furthermore, clear changes in the expression levels of genes involved in growth and development, accompanied by growth inhibition, were observed after co-treatment with MCRR and MCLR. In addition, zebrafish larvae subjected to MCRR and/or MCLR treatment showed increased levels of superoxide dismutase, glutathione, and malondialdehyde, and decreased levels of catalase in the MCRR + MCLR group, indicating oxidative stress and lipid peroxidation. Thus, we investigated the synergistic developmental toxicity of MCRR and MCLR during the early life stages of zebrafish development., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in the present experiment., (Copyright © 2023. Published by Elsevier Inc.)

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC 50 ) values of the embryos and larvae were 1.71 and 0.22 mg l -1 for copper and 2.57 and 2.72 mg l -1 for zinc, respectively, whereas the MB LC 50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l -1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l -1 for embryos and 0.03, 0.03 and 1.78 mg l -1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l -1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l -1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration., (© 2023 Fisheries Society of the British Isles.)

Newcastle disease (ND) and infectious bursal disease (IBD) are two viral infectious diseases that are extremely damaging to the poultry industry and are widespread throughout the world. It is necessary to develop a safe and effective vaccine against IBD and ND because vaccination is an effective preventive measure. It has been discovered that recombinant proteins expressed by an expression system in which a fragment of mammalian Immunoglobulin G (IgG) Fragment crystallizable (Fc) is linked to a segment of a gene have antibody-like properties that increase the exogenous protein's serum half-life. Heavy chain constant region 3 and heavy chain constant region 4 (CH3-CH4) of Avian Immunoglobulin Y (IgY) is structurally very similar to mammalian Ig G Fc. In this study, a bivalent vaccine rClone30-VP2L-CH3-CH4-GMCSF was developed by using NDV rClone30-chGM-CSF vector to produce VP2L-CH3-CH4 fusion protein. The vaccine has been given to 14-day-old specific pathogen free (SPF) free chickens to test whether it has the potential to prevent IBD and ND. Anti-IBDV and anti-NDV antibody levels in serum were evaluated using ELISA and HI, respectively, and the contents of CD4 + T, CD8 + T, and B cells in leukocytes were determined via flow cytometry. The contents and mRNA transcription levels of four inflammatory factors, IL-1β, IL-4, IFN-γ and chGM-CSF, were detected by ELISA and real-time PCR respectively. The results showed that after vaccination with the rClone30-VP2L-CH3-CH4-GMCSF vaccine, the levels of anti NDV and anti IBDV antibodies in chickens were significantly higher than those of the rClone30 vaccine and commercial vaccines. Meanwhile, the contents and transcription levels of inflammatory factors in chickens inoculated with rClone30-VP2L-CH3-CH4-GMCSF were significantly increased, and the proliferation response of B cells, CD4 + and CD8 + T cells was also stronger. However, the rClone30-VP2L-CH3-CH4-GMCSF vaccine had no significant advantage over the rClone30-VP2L-GMCSF vaccine in any of the above-mentioned features. In summary, rClone30-VP2L-CH3-CH4-GMCSF can stimulate the body to produce a stronger immune response, showing its potential to be considered as vaccine against IBD and ND, but the addition of CH3-CH4 did not improve the vaccine's immune effect as expected. The research lays the foundation for developing vaccines for other infectious viral diseases and avoids a unrealistic vaccine optimization method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67-20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED 50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both μ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain., Competing Interests: Declarations of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Acute pancreatitis (AP) is a common inflammatory disease of the pancreas with high mortality rates. It is of great significance to take scientific intervention measures for patients with AP in time., Aim: To explore the effect of standardized nursing combined with mindfulness stress reduction training on the curative effect, negative emotion, and quality of life in patients with acute pancreatitis., Methods: A total of 80 patients with acute pancreatitis admitted to The First People's Hospital of Jiangxia District Hospital from May 2021 to May 2023 were randomly divided into control group and observation group ( n = 40). Patients in control group were given the standardized nursing intervention, and the observation group were given standardized nursing plus mindfulness stress reduction training intervention. The time of clinical symptom disappeared or improved, complication occurrence rate, emotional state, and quality of life score of the two groups were observed and compared., Results: In comparison with the control group, the bowel sound recovery time, ventosity and abdominal pain improvement time, and venting and cacation time in observation group were shorter, and the total incidence rate of complications was reduced, showing statistically significant difference ( P < 0.05). The scores of anxiety and depression in observation group were lower than those in control group ( P < 0.05). Serum levels of tumour necrosis factor alpha, interleukin (IL)-6, IL-1β and IL-8 in observation group were lower than those in control group ( P < 0.05). The scores of life quality in physiology, psychology, environment and social relations in observation group were higher than those in control group, and the differences were statistically significant ( P < 0.05)., Conclusion: The application of standardized nursing intervention combined with mindfulness stress reduction training in patients with acute pancreatitis has a definite effect, which can help to ameliorate the clinical symptoms, anxiety and depression of patients, reduce the incidence rate of complications, and improve the prognosis of patients., Competing Interests: Conflict-of-interest statement: All the authors declared no conflict of interest existing in this paper., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Recently, BiCuOTe as a promising thermoelectric material has attracted extensive interest due to its lower thermal conductivity and higher electrical conductivity. However, little is known about the role of point defects in the growth, processing, and device degradation of this material. Moreover, the elastic properties which provide valuable information about the bonding characteristics, heat conductivity, and their anisotropic characters are investigated for effective design and characterization of new devices. Motivated by these considerations, a first-principles study about the stability of point defects and their effects on the thermal-mechanical properties of BiCuOTe was performed. The vacancies are found to be more stable than the interstitials. X O (here X occupying the O lattice site, with X = Cu, Bi or Te) are generally unfavorable among the considered point defects. Point defects generally have negative effects on elastic constants (except C 66 ), suggesting that the resistance of defective systems to uniaxial and shear deformation is usually weaker than the that of ideal BiCuOTe. Similarly, point defects could deteriorate the ability to resist external compression. However, the introduction of point defects may improve the elastic compliances and depress the Debye temperature, which may increase the thermal expansion efficient of BiCuOTe. As compared with the ideal system, the point defects such as Cu Bi , Te Bi , Bi Te , O Cu , Cu Te and Te Cu may generally reduce the phonon thermal conductivity. This study would provide insights into the effect of point defects on the elastic and thermal properties of BiCuOTe and has important implications in the rational design of superior thermoelectric materials.

Chitin deacetylase (CDA) can accelerate the conversion of chitin to chitosan, influencing the mechanical properties and permeability of the cuticle structures and the peritrophic membrane (PM) in insects. Putative Group V CDAs SeCDA6/7/8/9 (SeCDAs) were identified and characterized from beet armyworm Spodoptera exigua larvae. The cDNAs of SeCDAs contained open reading frames of 1164 bp, 1137 bp, 1158 bp and 1152 bp, respectively. The deduced protein sequences showed that SeCDAs are synthesized as preproteins of 387, 378, 385 and 383 amino acid residues, respectively. It was revealed via spatiotemporal expression analysis that SeCDAs were more abundant in the anterior region of the midgut. The SeCDAs were down-regulated after treatment with 20-hydroxyecdysone (20E). After treatment with a juvenile hormone analog (JHA), the expression of SeCDA6 and SeCDA8 was down-regulated; in contrast, the expression of SeCDA7 and SeCDA9 was up-regulated. After silencing SeCDAV (the conserved sequences of Group V CDAs) via RNA interference (RNAi), the layer of intestinal wall cells in the midgut became more compact and more evenly distributed. The vesicles in the midgut were small and more fragmented or disappeared after SeCDAs were silenced. Additionally, the PM structure was scarce, and the chitin microfilament structure was loose and chaotic. It was indicated in all of the above results that Group V CDAs are essential for the growth and structuring of the intestinal wall cell layer in the midgut of S. exigua . Additionally, the midgut tissue and the PM structure and composition were affected by Group V CDAs.

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study. In general, the inhibitors bearing a cyclic amine substituent at the 4-position of the quinolinium ring showed better antibacterial activity (MIC down to 0.25 μg/mL) than that at the 2-position, especially against Gram-positive bacteria. Among the twenty FtsZ inhibitors examined in various assays, A3 was identified to exhibit excellent antibacterial activity against S. aureus (MIC = 0.5-1 μg/mL), S. epidermidis (MIC = 0.25 μg/mL) and E. faecium (MIC = 1-8 μg/mL). More importantly, A3 showed low hemolytic toxicity (IC 5  = 64 μg/mL) and was found not readily to induce drug resistance. A3 at 2-8 μg/mL promoted the polymerization of FtsZ and interrupted the bacterial division. Furthermore, the ligand-FtsZ interaction study conducted with circular dichroism and molecular docking revealed that A3 induced secondary structure changes of FtsZ protein upon binding to the interdomain cleft of the protein. A3 is thus a potent inhibitor of FtsZ and shows potential to be used as a new antibacterial agent against drug-resistant bacteria., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The treatment of sewage sludge (SS) is an environmental problem worldwide. In recent years, hydrothermal carbonization (HTC) of SS for hydrochar (HC) has attracted extensive attention. This study preliminarily explored the microwave-assisted HTC of SS for the first time. Increasing the reaction temperature (150-250 °C) and reaction time (0-120 min) resulted in a decrease in the HC yield, and it gradually increased with the rising solid-liquid ratio (0.03-0.25 g/mL). Compared with raw SS, the HC products possessed higher aromaticity, carbonization degree, porosity, and polarity, and lower content of soluble nutrients (N/P/K) and leachable heavy metals (Cu, Zn, Pb, Cd, Cr, and Ni), indicating a lower risk of nutrient and heavy metal loss. Attention should be paid to the total contents of Zn and Cd in HC exceeded the permitted value for use in cultivated land with edible crops. The use of CaO as a catalyst improved the yield of HC, made the HC and process water (PW) weakly alkaline, and further passivated the heavy metals in the HC. In the case of H 3 PO 4 , although the conversion of SS was enhanced (lower content of volatile organic matter in HC), the contents of soluble nutrients (N/P/K) in HC/PW increased, and the migration of Zn and Cd into process water was enhanced. The HCs obtained in this study had poor combustion properties, but higher ignition temperatures than raw SS. PW must be properly treated or recycled because it still contained high contents of organic matter and nutrients. This fundamental study provides basic insights into the microwave-assisted HTC of SS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dried flowers of Inula britannica commercially serve as pharmaceutical/nutraceutical herbs in the manufacture of medicinal products and functional tea that has been reported to possess extensive biological property. However, the neuroprotective constituents in I. britannica flowers are not known. In the current study, phytochemicals of sesquiterpenoid-enriched I. britannica flowers extract and their potential multifunctional neuroprotective effects were investigated. Nineteen structurally diverse sesquiterpenoids, including two new sesquiterpenoid dimers, namely, inubritanolides A and B (1, 2), and four new sesquiterpenoid monomers (3-6), namely, 1-O-acetyl-6-O-chloracetylbritannilactone (3), 6-methoxybritannilactone (4), 1-hydroxy-10β-methoxy-4αH-1,10-secoeudesma-5(6),11(13)-dien-12,8β-olide (5) and 1-hydroxy-4αH-1,10-secoeudesma-5(6),10(14),11(13)-trien-12,8β-olide (6), as well as 13 known congeners (7-19) were isolated from this source. The structures of compounds 1-6 were elucidated by 1D- and 2D- NMR and HR-ESI-MS data, and their absolute configurations were discerned by electronic circular dichroism (ECD) data analysis and single crystal X-ray diffraction. Interestingly, inubritannolide A (1) is a new type [4 + 2] Diels-Alder dimer featuring a hepta-membered cycloether skeleton. Most of the compounds showed potential multifunctional neuroprotective effects, including antioxidative, anti-neuroinflammatory, and microglial polarization properties. Specifically, 1 and 6 displayed slight strong neuroprotective potency against different types of neuronal cells mediated by various inducers including H 2 O 2 , 6-hydroxydopamine (6-OHDA), and lipopolysaccharide (LPS). Overall, this is the first report on multifunctional neuroprotective effects of sesquiterpenoid-enriched I. britannica flowers extract, which supports its potential pharmaceutical/nutraceutical application in neurodegenerative diseases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta  = 8.36 × 10 -8 , OR = 1.29; rs7259428, 19q12, ZNF536, P meta  = 7.58 × 10 -8 , OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta  = 1.95 × 10 -8 ; rs2414487, 15q21.3, LOC145783, P meta  = 4.53 × 10 -9 ; rs2106525, 7q31.1, MDFIC, P meta  = 6.24 × 10 -9 ). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice., (© 2021. The Author(s).)

Background: Use of 0.01% atropine eye drops (0.01% A) is one of the most common treatments for myopia control for children in Asia. Auricular acupoint stimulation (AAS) was reported to enhance the effect of higher-concentration atropine (0.25%, 0.125%) on myopia control. This study was designed to compare the effect of 0.01% A combined with AAS and 0.01% A alone on myopia progression and choroidal thickness in children., Methods: A total of 104 children were stratified by age and randomly assigned at 1 : 1 to receive 0.01% A or 0.01% A + AAS treatment for 6 months. Repeated measurements of cycloplegic spherical equivalent (SE) autorefraction, axial length (AL), and choroidal thickness were performed at baseline, 1 month, 3 months, and 6 months., Results: The adjusted mean SE change over the 6 months was -0.38 ± 0.04 D in the 0.01% A group ( n  = 50) and -0.25 ± 0.04 D in the 0.01% A + AAS group ( n  = 50), demonstrating a significant between-group difference ( P  = 0.02). There was no statistically significant difference in the change of AL and choroidal thickness between the two groups (both P  > 0.05)., Conclusions: Adjunctive AAS compared with 0.01% A monotherapy slowed myopic progression in Chinese children by a statistically small amount, but had no effect on axial elongation and choroidal thickness during this 6-month observation. The trial is registered with ChiCTR1900021316., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Xie-He Kong et al.)

Ethnopharmacological Relevance: Si-Miao-Yong-An decoction (SMYAD) is a renowned traditional Chinese medicinal formula. SMYAD was originally recorded in the "Shi Shi Mi Lu", which was edited by medical scientist Chen Shi'duo during the Qing Dynasty. SMYAD has been traditionally used to treat thromboangiitis obliterans. At present, it is mainly used in clinical applications and research of cardiovascular diseases., Aim of the Study: To explore the effects of SMYAD on the pathological changes of atherosclerosis (AS) and the differentiation of monocytes, macrophages, and regulatory T (Treg) cells in apolipoprotein E knockout (ApoE -/- ) mice., Materials and Methods: Eight C57BL/6J mice, which were fed with normal diet for 16 weeks, were used as control group. Forty ApoE -/- mice were randomly divided into model group, atorvastatin group, SMYAD low-dose (SMYAD-LD) group, SMYAD medium-dose (SMYAD-MD) group, and SMYAD high-dose (SMYAD-HD) group. ApoE -/- mice were fed with western diet (WD) for 8 weeks, and the drugs were continuously administered for 8 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured by the esterase method. Morphological changes of the aortic sinus in mice were observed by hematoxylin-eosin (HE) staining, the lipid infiltration of the aorta and aortic sinus were observed by oil red O staining, and the spleen index was calculated. The proportion of Ly6C high and Ly6C low monocyte subsets, macrophages, and their M1 phenotype, as well as Treg cells in spleen were measured by flow cytometry. The expressions of cluster of differentiation 36 (CD36), scavenger receptor A1 (SRA1), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), F4/80, and fork head frame protein 3 (FOXP3) in aortic sinus were assessed by immunohistochemical staining. The serum levels of oxidized low density lipoprotein (ox-LDL), interleukin-1β (IL-1β), IL-18, transforming growth factor-β (TGF-β), and IL-10 were measured by enzyme-linked immunosorbent assays (ELISA)., Results: Compared with the model group, the level of serum TC and LDL-C decreased in the SMYAD group, the pathological changes of aortic sinus decreased, and lipid infiltration of aorta and aortic sinus also decreased. These decreases were accompanied by a significant downregulation of CD36, SRA1, and LOX-1. Furthermore, the proportions of Ly6C high pro-inflammatory monocyte subsets, macrophages, and their M1 phenotypes in spleen decreased significantly, while the proportion of Treg cells increased. In addition, while the expression of F4/80 decreased, the expression of FOXP3 increased in the aorta sinus. The levels of serum pro-inflammatory factors IL-1β and IL-18 decreased., Conclusions: SMYAD can improve the pathological changes associated with AS and can inhibit lipid deposition in ApoE -/- mice induced by WD diet. The likely mechanism is the inhibition of the differentiation and recruitment of monocytes and macrophages, the promotion of the differentiation and recruitment of Treg cells, as well as the reduction of the secretion of pro-inflammatory factors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Crohn's disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn's disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn's disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn's disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1β and IL-18 in the colon in Crohn's disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1β and ultimately suppressing colonic inflammation in Crohn's disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn's disease rats., Competing Interests: The authors have declared that no competing interests exist

Dimethyl sulfoxide (DMSO) is a universally used solvent in various synthetic reactions, and trace amounts of DMSO residual are often seen on the surface of chemical product. It is difficult to quickly determine whether the residual DMSO is washed completely. This work reports a Cd II metal-organic framework (MOF) SXU-4 which can detect trace amounts of DMSO in various solvents. Fluorescence experiments reveal its turn-on fluorescence effect toward DMSO with high selectivity and sensitivity, indicating that it can be used as an effective luminescent probe for rapid chemical product purity detection by testing the washing solution. Crystallographically characterized DMSO loaded SXU-4 (DMSO@SXU-4), in combination with computational results uncover that the enhanced DMSO-MOF conjugation through multiple DMSO-MOF supramolecule interactions and charge rearrangement are the main causes of fluorescence intensification., (© 2020 Wiley-VCH GmbH.)

A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery.

Three new quinazoline-containing diketopiperazines, polonimides A-C ( 1 - 3 ), along with four analogues ( 4 - 7 ), were obtained from the marine-derived fungus Penicillium polonicum . Among them, 2 and 4 , 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1 - 3 were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in 3 and 5 . All of 1 - 7 were tested for their chitinase inhibitory activity against Of Hex1 and Of Chi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1 - 7 exhibited weak activity towards Of Hex1 and strong activity towards Of Chi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%-10.3% and 79.1%-95.4%, respectively. Interestingly, 1 - 7 showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.

Objective: The goal of this study was to review relevant studies in order to determine the efficacy of decompression with fusion versus decompression in the treatment of lumbar spinal stenosis., Methods: Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we used odds ratios, mean difference (MD), and 95% confidence interval (95% CI) to assess and synthesize outcomes., Results: We found 13 studies that were consistent with this meta-analysis with a total of 29066 patients. Compared with decompression, decompression with fusion significantly increased the incidence of complications (RR: 1.41, 95%CI: 1.26-1.57), the length of hospital stay (WMD: 1.868, 95%CI: 1.394-2.343), operative time (WMD: 80.399, 95%CI: 44.397-116.401), estimated blood loss (WMD: 309.356, 95%CI: 98.008-520.704) and Zurich claudication questionnaire in symptom severity (WMD: 0.200, 95%CI: 0.006-0.394). The reoperation rate was lower in the decompression with fusion group than the decompression group but without significant difference (RR: 0.91, 95%CI: 0.82-1.00). There was no significant difference between 2 groups in visual analog scale (leg pain and back pain), ODI, Short Form 36 Health Survey physical component summary, Short Form 36 Health Survey mental component summary, and Zurich claudication questionnaire physical function., Conclusion: Decompression with fusion has no significant clinical advantages in treatment of lumbar spinal stenosis when compared with decompression.

Purpose: To compare the efficacy of right portal vein embolization using ethylene vinyl alcohol (EVOH-PVE) compared to other embolic agents and surgical right portal vein ligation (PVL). Material and methods: Patients with right sided liver malignancies scheduled for extensive surgery and receiving induction of liver hypertrophy via right portal vein embolization/ligature between 2010-2016 were retrospectively evaluated. Treatments included were ethylene vinyl alcohol copolymer (Onyx®, EVOH-PVE), ethiodized oil (Lipiodol ® , Lipiodol/PVA-PVE), polyvinyl alcohol (PVA-PVE) or surgical ligature (PVL). Liver segments S2/3 were used to assess hypertrophy. Primary outcome was future liver remnant growth in ml/day. Results: Forty-one patients were included (EVOH-PVE n =  11; Lipiodol/PVA-PVE n =  10; PVA-PVE n =  8; PVL n =  12), the majority presenting with cholangiocarcinoma and colorectal metastases ( n =  11; n =  27). Pre-interventional liver volumes were comparable ( p =  .095). Liver hypertrophy was successfully induced in all but one patient receiving Lipiodol/PVA-PVE. Liver segment S2/3 growth was largest for EVOH-PVE (5.38 ml/d) followed by PVA-PVE (2.5 ml/d), with significantly higher growth rates than PVL (1.24 ml/d; p <  .001; p =  .007). No significant difference was evident for Lipiodol/PVA-PVE (1.43 ml/d, p =  .809). Conclusions: Portal vein embolization using EVOH demonstrates fastest S2/3 growth rates compared to other embolic agents and PVL, potentially due to its permanent portal vein embolization and induction of hepatic inflammation.

This study aimed to investigate the molecular mechanisms underlying the roles of metformin (MET) and Sorafenib (SOR) in the treatment of endometrial hyperplasia (EH) in polycystic ovary syndrome (PCOS). Effects of MET and SOR on the area of endometrium and myometrium were detected. Western blot analysis and immunohistochemistry assays were carried out to detect the levels of mammalian target of rapamycin complex 1 (mTORC1), mTORC2, LC3-II, P62, and Caspase-3 in rats and cultured cells. Furthermore, cell counting kit-8 assay and flow cytometry analysis was carried out to determine the apoptotic profiles of treated cells. MET and SOR could apparently decrease the areas of endometrium and myometrium in PCOS. MET notably enhanced the expression of LC3-II and Caspase-3 in PCOS while substantially reducing the level of mTORC1 and P62. Similarly, SOR also enhanced the expression of LC3-II and Caspase-3 in PCOS while substantially reducing the level of mTORC2 and P62. Treatment with MET and SOR significantly inhibited the proliferation of HCC-94 and HEC-1-A cells while promoting their apoptosis by upregulating the expression of Caspase-3. In cells treated with MET, the expression of mTORC1 and LC3-II was upregulated while the expression of P62 was downregulated. Similarly, in cells treated with SOR, the expression of mTORC2 and LC3-II was also upregulated while the expression of P62 was also downregulated. Furthermore, MET showed no effect on mTORC2 expression, while SOR showed no effect on mTORC1 expression. In this study, we suggested that MET and SOR alleviated the risk of EH in PCOS via the mTORC1/autophagy/apoptosis axis and mTORC2/autophagy/apoptosis axis, respectively., (© 2019 Wiley Periodicals, Inc.)

A novel acidogenic phosphorus recovery (APR) process was developed in combination with Fe(III)-based chemical phosphorus removal and a membrane bioreactor (MBR) for enhanced wastewater treatment and effective P recovery. Two different system configurations were evaluated: Fe-dosing MBR (Fe-MBR), with the Fe-dosing into the MBR, and Fe-enhanced primary sedimentation followed by the MBR (FeP-MBR). The results show that both systems performed well for enhanced nutrient (N and P) removals and P recovery, with approximately 50% of the total P recovered from the municipal wastewater in the form of vivianite. Compared to the Fe-MBR system, FeP-MBR achieved more efficient P recovery under low food-waste loading conditions, maintained a higher ratio of biomass in activated sludge and experienced a slower rate of membrane fouling. Important functional bacteria were identified, including Prevotella and Selenomonas, which are active in hydrolysis and acidogenesis of sludge, and Aeromonas and Sulfurospirillum, which are involved in dissimilatory iron reduction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cardiovascular disease is the major cause of death in patients with diabetes. Current treatment strategies for diabetes rely on lifestyle changes and glucose control to prevent angiopathy and organ failure. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used as an add-on therapy to insulin treatment. Exenatide also has multiple beneficial effects in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion. However, the mechanisms underlying the cardioprotective effects of exenatide in diabetes have not been fully clarified. To address this issue, we investigated the cardioprotective effects of exenatide in type 1 and type 2 diabetic mice. We found that exenatide simultaneously attenuated reactive oxidative species (ROS) production through increases in the antioxidant enzymes manganese dependent superoxide dismutase (MnSOD) and catalase. Moreover, exenatide decreased tumor protein P53 (p53) expression and prevented cell apoptosis in H9c2 cells. The presence of the catalase inhibitor 3-AT attenuated the effects of exenatide. Overall, the results strongly indicate that exenatide treatment may be protective against the development of diabetic cardiomyopathy.

The outgrowth and metastasis of cervical cancer (CC) contribute to its malignancy. Pituitary Tumor Transforming Gene 1 (PTTG1) is upregulated in many types of cancer, and enhances tumor cell growth and metastasis. However, the activation and regulation of PTTG1 in CC, especially by its pseudogene PTTG3P, have not been shown. Here, we detected significantly higher levels of PTTG1 and PTTG3P in the resected CC tissue, compared to the paired adjacent normal cervical tissue. Interestingly, the PTTG3P levels positively correlated with the PTTG1 levels. High PTTG3P levels were associated with poor patients' survival. In vitro, PTTG1 were increased by PTTG3P overexpression, but was inhibited by PTTG3P depletion in CC cells. However, PTTG3P levels were not altered by modulation of PTTG1 in CC cells, suggesting that PTTG3P is upstream of PTTG1. Moreover, PTTG3P increased CC cell growth, likely through CCNB1-mediated increase in cell proliferation, rather than through decrease in cell apoptosis. Furthermore, PTTG3P increased CC cell invasiveness, likely through upregulation of SNAIL and downregulation of E-cadherin. Our work thus suggests that PTTG3P may promote growth and metastasis of CC through PTTG1.

A systematic chemical exploration of the marine-derived fungus Penicillium janthinellum led to the isolation of four indole-diterpenoid derivatives ( 1 - 4 ), including new penijanthines C and D ( 1 and 2 ), and a pair of new steroidal epimers, penijanthoids A and B ( 5 and 6 ). The calculated ECD spectra and Snatzke's method for the new compound 1 were carried out to determine its absolute configuration. The absolute configuration of 3 was established by X-ray diffraction and calculated ECD methods for the first time. DP4plus approach was used to elucidate the absolute configurations of the C-25 epimeric steroids 5 and 6 . 25-Epimeric 5 and 6 represent the first examples of steroids forming a five-membered lactone between C-23 and C-27 from marine fungi. Compounds 1 , 2 , 5 , and 6 displayed significant anti- Vibrio activity (Minimum inhibitory concentration, MIC values ranging from 3.1 to 50.0 μM) against three pathogenic Vibrio spp.

Beclin 1 is involved in autophagy, differentiation, apoptosis and cancer progression, and functions as a haploinsufficient tumor suppressor gene. The aim of the present study was to elucidate the function of Beclin 1 in colon cancer. A Beclin 1-expressing plasmid was transfected into HCT-15 and HCT-116 cells, and the phenotypes and associated molecules were determined. Beclin 1 transfectants were subcutaneously injected into nude mice to determine tumor growth, and proliferation and apoptosis levels using Ki-67 immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. Beclin 1 overexpression inhibited viability as determined using a Cell Counting Kit-8 assay, inhibited migration and invasion as determined using a wound healing assay or Transwell assay, and lamellipodia formation by filamentous actin staining, induced autophagy as determined using electron microscopy, and light chain 3B (LC-3B) expression, and apoptosis as determined using Annexin V staining in the two cell lines (P<0.05). Beclin 1 induced G 2 arrest of HCT-15 transfectants as determined using propidium iodide staining (P<0.05), whereas HCT-116 transfectants were arrested in G 1 phase (P<0.05). The two transfectants exhibited increased expression of c-Myc, cyclin D1, β-catenin, insulin-response element 1 and 78 kDa glucose-regulated protein compared with the control and mock cells as determined using the reverse transcription-quantitative polymerase chain reaction (P<0.05). Beclin 1 overexpression upregulated LC-3B and cyclin-dependent kinase 4 expression, but downregulated cyclin E expression of the cancer cell lines as determined using western blot analysis (P<0.05). Beclin 1 expression in vivo significantly suppressed the proliferation of colon cancer cells in xenograft models via inducing apoptosis by TUNEL, and inhibiting proliferation by Ki-67 expression (P<0.05). Beclin 1 overexpression may reverse aggressive phenotypes and suppress colon cancer tumor growth, and be employed as a target molecule for gene therapy of patients with colon cancer.

Fibroblast growth factor-21 (FGF-21), an endocrine hormone, is regarded as a therapeutic target for diabetes base on its potent effects on improving hyperglycemia. Sodium-dependent glucose cotransporter 1 (SGLT1) is mainly expressed in the small intestine (SI) for intestinal glucose absorption. It has been demonstrated that SGLT1 expression is increased in diabetes, which is thought to contribute to the rapidly rising postprandial blood glucose levels. Thus, we aim to examine whether FGF-21 regulates expression of intestinal SGLT1 in diabetes. The db/db mice were treated with insulin, low and high dose of FGF-21 for 5 weeks and then measured changes in glucose metabolism, intestinal glucose absorption and SGLT1 expression. The results showed that FGF-21 improved glucose homeostasis, inhibited intestinal glucose uptake and reduced intestinal SGLT1 expression compared with insulin in db/db mice. To further explore the mechanism of effects of FGF-21 on SGLT1 expression. The murine intestinal epithelial MODE-K cells were treated with FGF-21 for 3 h, 6 h, 12 h and 24 h and then measured glucose uptake, SGLT1 expression, another glucose transporter GLUT2 expression and associated mechanism. Our results showed that FGF-21 inhibited glucose uptake and reduced SGLT1 expression in MODE-K cells, which were due to inactivating SGK-1 pathway. Moreover, above effects of FGF-21 on MODE-K cells were abolished by PD173074, a FGFR1 inhibitor. In conclusion, FGF-21 regulates glucose level in diabetes partially due to inhibiting glucose absorption in the SI via inactivating SGK-1 pathway. These results expand our knowledge about how FGF-21 regulates glucose metabolism., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Macrophages are paramount to the initiation and procession of atherosclerosis, thus targeting macrophages in the progress of atherosclerosis is indispensable. Therefore, we perform in vitro experiments to investigate the effects of FGF-21 on macrophages in the progress of atherosclerosis. First, we use phorbol-12-myristate-13-acetate (PMA), a phorbol ester, to induce THP-1 cells into macrophages as macrophages model. After that we use Ox-LDL to induce macrophages into foam cells and simultaneously administrate with FGF-21 or not to determine whether FGF-21 has effects on foam cells formation and related inflammatory response. Wound healing results show that FGF-21 can inhibit macrophage migration. Oil Red-O stain, immunofluorescence and flow cytometer results show that FGF-21 can repress cholesterol accumulation in macrophages thereby inhibit foam cells formation and these effects can be abolished by FGFR inhibitor. Moreover, real-time PCR results showed that FGF-21 significantly reduces expression of inflammatory factors including IL-1α, IL-6 and TNF-α and this effect can be abolished by FGFR inhibitor. Furthermore, to determine the mechanism of FGF-21 regulates inflammatory response in Ox-LDL-induced THP-1 macrophages, western blotting results show that after treatment of Ox-LDL in macrophages, NF-κB signaling pathway is activated but FGF-21 can significantly inhibit this pathway. In addition, FGF-21 also regulates some regulators of lipid metabolism after treatment of Ox-LDL in macrophages. Above all, our findings demonstrate that FGF-21 can regulate foam cells formation, macrophage migration, inflammatory response and lipid metabolism in Ox-LDL-induced THP-1 macrophages., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: This study aims to investigate the role of three-dimensional visualization technique in the diagnosis and treatment of progressive hilar cholangiocarcinoma., Methods: From January 2014 to February 2017, a three-dimensional visualization model was set up in 23 patients with progressive hilar cholangiocarcinoma. The distributions and variations of the hepatic portal ducts were observed. The tumors were classified based on Bismuth classification. The simulation operation was performed and the operation plan was established., Results: All 23 patients revealed a clear relationship between the intrahepatic and extrahepatic ducts, as well as the tumors and ducts. An individualized surgery program was established through the accurate calculation of liver volume and residual liver volume. Among these patients, 13 patients completed radical resection of hilar cholangiocarcinoma combined with massive hepatectomy. No bile leakage occurred and no operative death was found., Conclusion: For patients with progressive hilar cholangiocarcinoma, the optimized three-dimensional visualization technique can accurately demonstrate the dilated biliary tract system, provide a new standard to determine the presence of tumor and peripheral vascular invasion, help in establishing a reasonable individualized operation plan, reduce the incidence of bile leakage and liver failure after the operation, and improve the success rate of operation., Competing Interests: None.

Fermentation of both glucose and xylose is essential to realize efficient bioconversion of renewable and abundant lignocellulosic biomass to hydrogen. In this study, a mixture of glucose and xylose at different ratios was used as a substrate for biological hydrogen production by an anaerobic sequential batch reactor (ASBR). An average glucose and xylose consumption of 80% and 50% with a high hydrogen production rate of 7.1 ± 0.9 mmol L -1 h -1 was obtained, respectively. Hydraulic retention time (HRT) played a critical role in hydrogen production at high glucose to xylose ratios. A maximum hydrogen production rate of 8.9 mmol L -1 h -1 was achieved at an optimized HRT of 12 h with a high glucose and xylose consumption of 92.2% and 82.2%, respectively. Upon further energy conversion analysis, continuous hydrogen production by ASBR provided the maximum energy conversion efficiency of 21.5%. These results indicate that ASBR can effectively accelerate the hydrogen production rate, improve substrate consumption regardless of the glucose to xylose ratio, and thus provides a new direction for efficient hydrogen production from lignocellulosic feedstock., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Up to 62% of perimenopausal women have depression symptoms. However, there is no efficacy treatment. The aim of this study is to compare the clinical efficacy and safety of EA therapy and escitalopram on perimenopause women with mild-moderate depressive symptom., Method: A multicenter, randomized, positive-controlled clinical trial was conducted at 6 hospitals in China. 242 perimenopause women with mild-moderate depressive symptom were recruited and randomly assigned to receive 36 sessions of EA treatment or escitalopram treatment. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome measures include menopause-specific quality of life (MENQOL) and serum sexual hormones which include estrogen, follicle-stimulating hormone, and luteinizing hormone., Results: 221 (91.3%) completed the study, including 116 in the EA group and 105 in the escitalopram group. The baseline levels of demographic and outcome measurements were similar in the two groups. In the intervention period, there was no difference between two groups. However, in the follow-up, both HAMD-17 and MENQOL were significantly decreased, and at week 24 the mean differences were -2.23 and -8.97, respectively. There were no significant differences in the change of serum sexual hormones between the two groups. No serious adverse events occurred., Conclusion: EA treatment is effective and safe in relieving depression symptom and improving the quality of life in the perimenopausal depression. Further research is needed to understand long-term efficacy and explore the mechanism of this intervention. This study is registered with ClinicalTrials.gov NCT02423694.

This paper reports a simple method used to fabricate a stretchable conductive polypyrrole (PPy) rough pore-shape polydimethylsiloxane (p-PDMS) device. An abrasive paper is first used to imprint rough micro-structures on the SU-8 micromold. The p-PDMS microchannel is then fabricated using a standard soft-lithography process. An oxygen plasma treatment is then applied to form an irreversible sealing between the microchannel and a blank cover PDMS. The conductive layer is formed by injecting the PPy mixture into the microchannel which polymerizes in the rough pore-shape micro-structures; The PPy/p-PDMS hybrid device shows good electrical property and stretchability. The electrical properties of different geometrical designs of the PPy/p-PDMS microchannel under stretching were investigated, including straight, curved, and serpentine. Mouse embryonic fibroblasts (NIH/3 T3) were also cultured inside the PPy/p-PDMS device to demonstrate good biocompatibility and feasibility using the conductive and stretchable microchannel in cell culture microfluidics applications. Finally, cyclic stretching and bending tests were performed to evaluate the reliability of PPy/p-PDMS microchannel.

Type 2 diabetes mellitus (T2DM) is accompanied by abnormal glucose metabolism and low-grade chronic inflammation. Fibroblast growth factor 21 (FGF-21) is a novel metabolic regulator and can function as an endocrine hormone to regulate glucose and lipid metabolism. Recently, FGF-21 was found to have anti-inflammatory effect, to our knowledge, the effect of FGF-21 on inflammatory state in diabetes has not been elucidated. Here, we use db/db mice as a Type 2 diabetes model to determine whether FGF-21 alleviates inflammatory state while improves hyperglycemia. Our results demonstrated that FGF-21 not only showed potent long lasting hypoglycemic effect, but also demonstrated strong anti-inflammatory effect in the serum and white adipose tissue. Besides, in vitro experiments, insulin resistance (IR) was induced in 3T3-L1 adipocytes by treating with TNF-α. Our results showed that TNF-α impaired glucose metabolism of 3T3-L1 adipocytes but FGF-21 repressed gene expression of inflammatory factors caused by IR and consequently improved the glucose metabolism in 3T3-L1 adipocytes. Furthermore, FGF-21 ameliorated glucose uptake of TNF-α-induced IR in 3T3-L1 adipocytes by inhibiting NF-κB signaling pathway., (Copyright © 2018. Published by Elsevier B.V.)

In this study, ZnO nanotubes (ZNTs) were prepared onto fluorine-doped tin oxide (FTO) glass and used as supports for MIPs arrays fabrication. Due to the imprinted cavities are always located at both inner and outer surface of ZNTs, these ZNTs supported MIPs arrays have good accessibility towards template and can be used as sensing materials for chemical sensors with high sensitivity, excellent selectivity and fast response. Using K 3 [Fe(CN) 6 ] as electron probe, the fabricated electrochemical sensor shows two linear dynamic ranges (0.02-5μM and 10-800μM) towards dopamine. This proposed electrochemical sensor has been applied for dopamine determination with satisfied recoveries and precision. More complex human urine samples also confirmed that the proposed method has good accuracy for dopamine determination in real biological samples. These results suggest potential applicability of the proposed method and sensor in important molecule analysis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Marsdeniae tenacissimae extract (MTE) has been used as an adjuvant medicine for cancer therapy for a long time. Although massive studies demonstrated its considerable anti-cancer effect, there is no research on its influence on erythrocytes, which are firstly interacted with MTE in the circulation. To investigate the influence of MTE on erythrocytes, we used a flow cytometer to detect the MTE-treated alternations of morphology, calcium concentration, and reactive oxygen species (ROS) level in erythrocytes. We used hemolysis under different osmotic solutions to evaluate the fragility of erythrocytes. Data showed that MTE treatment dose-dependently increased the ratio of erythrocyte fragmentation (P<0.001) and shrinking, and elevated the forward scatter (FSC) value (P<0.001) and calcium accumulation (P<0.001). MTE induced ROS production of erythrocytes under the high glucose condition (P<0.01) and consequently caused a rise in fragility (P<0.05). These results suggest that MTE induces cytotoxicity and aging in erythrocytes in a dose-dependent manner, and presents the possibility of impairment on cancer patients' circulating erythrocytes when MTE is used as an anti-cancer adjuvant medicine.

In this work, a selective sample cleanup procedure that combined molecular imprinting technique with solid phase extraction was developed for the simultaneous extraction of the seven nitroimidazoles (NMZs) from honey samples. The molecular imprinting polymers for NMZs were prepared through bulk polymerization method using 2-methyl-5-nitroimidazole as template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross linking agent. The obtained molecular imprinting polymers showed high affinity to template molecule and was used as selective sorbent for simultaneously selective extraction of the seven NMZs from honey matrix. An off-line molecularly imprinted solid phase extraction (MISPE) method followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) for simultaneous determination of the seven NMZs from honey samples was also established. The proposed method was validated at 1.0, 2.0 and 10.0μg/kg, obtaining recoveries in the range of 79.7-110%, with repeatability and interday precision values (expressed as relative standard deviation) ≤11.4% and ≤15.2%, respectively. Limits of quantification for different NMZs were 1.0μg/kg, which were always below the minimum required performance limits established by the European Community Reference Laboratories (Commission Decision 2002/657/EC). It was demonstrated that this proposed MISPE-HPLC-MS-MS method could be applied to direct determination of NMZs from honey samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Surgery remains the first choice of treatment for tongue cancer. Immediate reconstruction should be performed after wide resection of tumour. The aim of this study was to evaluate the anterolateral thigh flap for reconstruction of lingual defects., Methods: We report 39 consecutive oral tongue squamous cell carcinoma patients who underwent lingual reconstruction with the anterolateral thigh flap between 2009 and 2010., Results: The width of the skin island was 4 to 5 cm and the length of the skin island was 6 to 8 cm in 31 patients with T2 tumour, while the width of the skin island was 5.5 to 6 cm and the length of the skin island was 9 to 12 cm in 8 patients with T3/4 tumours. The all flap survival rate was 97.5 % in our series., Conclusions: We could obtain sufficient flap volume using the anterolateral thigh flap for tongue reconstruction. The single perforator-based anterolateral thigh flap is a good option for soft tissue reconstruction in patients with oral tongue squamous cell carcinoma.

Aim: To explore the relationship of clinicopathological features and the proteins of C-met expression in the prognosis of cholangiocarcinoma., Methods: Clinical data and the completed follow-up information of patients with cholangiocarcinoma who underwent cholangiocarcinoma operation from January 2004 to December 2010 were analyzed retrospectively. The relationship of clinicopathological features and C-met in the prognosis of the patients was analyzed., Results: Patients with high expression of C-met had significantly shorter overall survival than those with low expression of C-met, the difference being statistically significant (P = .003). Patients with high C-met expression had significantly shorter disease-free survival time than those with low expression of C-met, the difference being statistically significant (P = .009). By COX multivariate analysis, high C-met expression in tumor tissues was an independent risk factor in predicting overall survival and disease-free survival for patients with cholangiocarcinoma (P = .038, .048, relative risk = 1.390, 1.427)., Conclusion: Patients with high C-met expression in cancer tissues had shorter disease-free survival and overall survival. High expression of C-met is an independent risk factor for overall survival and disease-free survival., (© The Author(s) 2015.)

The purpose of this study was to screen for genes that were differentially expressed between a human gastric carcinoma cell line (HGC-27) and their tumor spheres, using the gene chip technique. The HGC-27 cells and tumor sphere cells were cultured in vitro in a sterile environment. Total RNA was extracted from both samples and purified using a standard TRIzol reagent. Total RNA was then hybridized onto a GeneChip, according to the standard protocols provided by the manufacturers of the GeneChip IVT Express Kit. The resulting fluorescence signals were analyzed and displayed using the Cluster and Treeview software programs. Under the criteria for significant differential expression (≥2-fold difference), 610 up- and 1135 down-regulated genes were identified in tumor sphere cells, compared to HCG-27 cells. These genes were involved in cell growth, signal transduction, tumorigenesis, and many other functional aspects of tumor cells. In conclusion, a number of genes were differentially expressed in tumor sphere cells compared to HCG-27 cells. In addition, we identified a close correlation between tumor sphere cells and tumorigenesis.

Mechanical stimulation is crucial to bone growth and triggers osteogenic differentiation through a process involving Rho and protein kinase A. We previously cloned a gene (AKAP13, aka BRX) encoding a protein kinase A-anchoring protein in the N-terminus, a guanine nucleotide-exchange factor for RhoA in the mid-section, coupled to a carboxyl region that binds to estrogen and glucocorticoid nuclear receptors. Because of the critical role of Rho, estrogen, and glucocorticoids in bone remodeling, we examined the multifunctional role of Akap13. Akap13 was expressed in bone, and mice haploinsufficient for Akap13 (Akap13(+/-)) displayed reduced bone mineral density, reduced bone volume/total volume, and trabecular number, and increased trabecular spacing; resembling the changes observed in osteoporotic bone. Consistent with the osteoporotic phenotype, Colony forming unit-fibroblast numbers were diminished in Akap13(+/-) mice, as were osteoblast numbers and extracellular matrix production when compared to control littermates. Transcripts of Runx2, an essential transcription factor for the osteogenic lineage, and alkaline phosphatase (Alp), an indicator of osteogenic commitment, were both reduced in femora of Akap13(+/-) mice. Knockdown of Akap13 reduced levels of Runx2 and Alp transcripts in immortalized bone marrow stem cells. These findings suggest that Akap13 haploinsufficient mice have a deficiency in early osteogenesis with a corresponding reduction in osteoblast number, but no impairment of mature osteoblast activity., (© 2015 American Society for Bone and Mineral Research.)

Background: Cholangiocarcinoma is one of the most common malignancies in China. Surgical resection is the only treatment option; however, diagnosis at advanced stage precludes surgery. Comprehensive knowledge of prognostic markers is missing. Hence, the aim of this study was to determine clinicopathological indexes that would be indicative of prognosis in post-operative cases of cholangiocarcinoma., Material and Methods: A retrospective analysis of 293 cases of cholangiocarcinoma patients attending the 301 Military Hospital in Beijing, China between January 2004 and December 2010 were included in the study. The patients had follow-up history until August 2012. Cox proportional hazards model analysis was performed to identify indexes of prognosis. All indicators were analyzed by univariate and multivariate analysis., Results: The median follow-up time was 55.90 months, with recurrence and metastasis in 162 cases (55.3%) and death in 223 cases (76.1%). The 1-year, 3-year, and 5-year survival rates were 71.7%, 38.2%, and 10.6%, respectively. The independent risk factors of overall survival were degree of tumor differentiation, TNM stage, surgical margin, intraoperative blood transfusion, tumor location, alkaline phosphatase levels in blood, and relapse., Conclusions: Good prognosis in cholangiocarcinoma patients is indicated by highly differentiated tumor, early stages of TNM staging, no resection margin invaded, no intraoperative blood transfusion, intrahepatic tumor, normal alkaline phosphatase levels, and no relapse.

Objective: To determine the optimum treatment for viral myocarditis (VMC)., Methods: A total of 126 VMC patients were randomly divided into the control group (42 cases) that was treated with conventional Western medicine, and the intervention group (84 cases) that was treated with a combination of Chinese medicine (CM) and Western medicine intervention termed optimum proposal of integration of disease and syndrome (OPIDS). Before and after 4 weeks of treatment, the integral of CM syndrome, self-rating depression and anxiety scales (SDS and SAS, respectively), echocardiograms (ECGs), heart rate variability and left ventricular systolic function were observed., Results: Compared with the control group, the intervention group showed significant reductions on the SDS and SAS (P <0.05); improvement of premature ventricular beats, atrioventricular blocks, ST-segment abnormalities, and significant T wave changes (P <0.05); greater reductions in standard deviation of NN intervals (SDNN), standard deviation for per 5 min averages NN intervals (SDANN), and root-mean-square of successive difference of NN intervals (rMSSD) (P <0.05); and increases in cardiac output, stroke volume, and ejection fraction, the last of which was statistically significant (P <0.05). Overall, the treatment efficacy rate was significantly better P<0.05) in the intervention group (75.61%) compared with the control group (69.70%)., Conclusion: OPIDS is quite effective in treating VMC and improves symptoms such as anxiety and depression, left ventricular systolic dysfunction, premature ventricular contraction, and cardiac autonomic nervous system dysfunction. [, Registration: Chinese clinical trial center (No. ChiCTR-TRC-00000298)].